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An autosomal dominant, qualitative platelet disorder associated with
multimerin deficiency, abnormalities in platelet factor V, thrombospondin,
von Willebrand factor, and fibrinogen and an epinephrine aggregation defect
CP Hayward, GE Rivard, WH Kane, J Drouin, S Zheng, JC Moore and JG Kelton
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Multimerin is a massive soluble, multimeric protein found in platelets and
endothelial cells. Recent studies identified multimerin as a specific
coagulation factor V binding protein, complexed with platelet, but not
plasma, factor V. These findings led us to investigate individuals with
inherited factor V deficiencies for possible multimerin abnormalities.
Platelet proteins were evaluated using immunoassays, sodium dodecyl
sulfate-polyacrylamide gel electrophoresis, immunoblotting,
immunoprecipitation, and direct binding studies. Patients with factor V
Quebec, a disorder with abnormal platelet factor V, had a quantitative
deficiency in multimerin (n = 11 tested; mean, 12.5%; range, 5% to 27% of
the normal pool; normal range, 45% to 214%) with a normal multimer pattern.
Quantitative and qualitative abnormalities were detected in their platelet
factor V. An unrelated patient who was deficient in platelet and plasma
factor V had normal platelet multimerin. The levels of platelet beta-
thromboglobulin, von Willebrand factor, thrombospondin, and fibrinogen
antigen were normal in the factor V Quebec patients. However, proteins with
abnormal mobility were detected in their platelet lysate and releasate, and
their platelet thrombospondin, von Willebrand factor, and fibrinogen showed
evidence of proteolytic degradation. Platelet counts of the factor V Quebec
patients ranged from mildly thrombocytopenic to low normal (mean, 159 x
10(9)/L; range, 104 to 198 x 10(9)/L). In addition, their platelets failed
to aggregate in response to 6 to 10 micromol/L epinephrine despite normal
numbers of platelet alpha 2-adrenergic receptors. These data indicate that
patients with factor V Quebec have an inherited bleeding disorder distinct
from other platelet disorders and associated with multiple abnormalities,
including multimerin deficiency, abnormal platelet factor V,
thrombospondin, von Willebrand factor, and fibrinogen, and an epinephrine
aggregation defect.
Volume 87,
Issue 12,
pp. 4967-4978,
06/15/1996
Copyright © 1996 by The American Society of Hematology
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